STF-31 | GLUT1/NAMPT inhibitor

STF-31 (724741-75-7) is an inhibitor of glucose transporter 1 (GLUT1; IC₅₀ = 1 μM)¹ and NAMPT³. It has been shown to kill renal cell carcinoma cells (the majority of which lack the von Hippel-Lindau suppressor gene) without toxicity to normal cells. The target of STF-31 anti-tumor activity has recently been questioned via use of large-scale cancer cell-line profiling.² This profiling indicated that nicotinamide phosphoribosyltransferase (NAMPT) was in fact the target of STF-31. The inhibition of NAMPT by STF-31 was confirmed via biochemical assay against recombinant NAMPT. The ability of STF-31 to inhibit NAMPT had been previously displayed (IC₅₀ = 19 nM).³ More recent experiments provide evidence that STF-31 has a dual function and inhibits both GLUT1 and NAMPT in a concentration-dependent manner.⁴

References/Citations:

1) Chan et al. (2011), Targeting GLUT1 and the Warburg effect in renal cell carcinoma by chemical synthetic lethality; Sci. Transl. Med., 3 94ra70
2) Adams et al., (2014), NAMPT is the Cellular Target of STF-31-Like Small-Molecule Probes; ACS Chem. Biol., 9 2447
3) Dragovich et al. (2014), Fragment-based design of 3-aminopyridine-derived amides as potent inhibitors of human nicotinamide phosphribosyltransferase (NAMPT); Bioorg. Med. Chem. Lett., 24 954
4)Kraus et al. (2018), Targeting glucose transport and the NAD pathway in tumor cells with STF-31: a re-evaluation; Cell Oncol.(Dordr) 41 485